The first tricyclic antidepressant in history was imipramine, which appeared in 1951. Although this and other tricyclics were the most widely used drugs for treating depression for many decades, they were gradually replaced by other more effective drugs, although imipramine is still used for certain disorders, not just depressive ones.

In this article we will analyze in detail the most important therapeutic uses and side effects of imipramine . We will also describe the key pharmacological properties of this drug and explain in which cases its consumption is contraindicated.

What is imipramine?

Imipramine is an antidepressant medication from the tricyclic class , which also includes clomipramine, amitriptyline, doxepin, nortriptyline, or desipramine. Imipramine was the first of these drugs to be developed; the initial purpose was its use as a sedative in cases of schizophrenia and as an antihistamine.

Tricyclic antidepressants were for a long time the drug treatment of choice in cases of depression. However, they have now been relegated to the background because of the emergence of selective serotonin reuptake inhibitors (SSRIs) and other drugs with higher degrees of specificity and tolerability.

The effects of imipramine are very broad, so it acts on different neurotransmitters; this explains both its therapeutic properties and the adverse reactions associated with its consumption. Especially relevant are its agonist effects on serotonin and noradrenaline , which occur through the inhibition of their reuptake.

Although imipramine has been marketed under different generic names, the best known of all is “Tofranil” since this brand name popularized the product and is still sold in many countries today.

Therapeutic uses of this drug

Imipramine, like the other drugs in the tricyclic class, is used mostly to treat symptoms on the spectrum of depression. Research suggests that it is especially useful in cases where depression is associated with anxiety-type symptoms , particularly psychomotor agitation.

In this regard, imipramine is sometimes prescribed to people with disorders such as major depression, dysthymia (chronic and mild depression with marked anxiety), bipolar disorder, panic disorder, and agoraphobia. It has also been applied in cases of attention deficit hyperactivity disorder, better known by the abbreviation “ADHD”.

The use of imipramine in the treatment of nocturnal enuresis is also relatively common. Its efficacy in this disorder is due to the fact that this drug reduces the proportion of slow wave sleep phases, and it is in these that the episodes of involuntary urination normally take place.

Adverse reactions and side effects

The most common adverse reactions associated with imipramine treatment include drowsiness , dizziness, tachycardia, dry mouth , urinary retention and orthostatic hypotension (sudden drop in blood pressure). There are also changes in brain electrical activity, such as those related to sleep.

Other signs affecting the central nervous system that are somewhat less frequent are anxiety, agitation, insomnia, nightmares, headaches, confusion or the appearance of tremors, convulsions and other motor symptoms related mainly to the extrapyramidal system.

Imipramine also causes other physiological side effects . These include cardiovascular disorders (hypertension, palpitations, dysrhythmias…), blurred vision, nausea, vomiting, increased appetite, gastrointestinal discomfort (such as cramps), constipation, jaundice and pupil dilation or mydriasis.

Overdose of imipramine or other tricyclic antidepressants causes blurred vision, mydriasis, confusion, drowsiness, and increased heart rate. The toxic dose is easier to reach for children, and sometimes death may occur from cardiac arrest if the disorders are not resolved quickly.

Contraindications and precautions

Even compared to other tricyclic antidepressants, imipramine has a very intense pharmacological potency. Because of this and its interaction with receptors for multiple types of neurotransmitter, the use of imipramine should be avoided in many and varied circumstances.

This drug is contraindicated in people with a history of disorders such as alcoholism, hyperthyroidism, diabetes , glaucoma, kidney and liver problems, epilepsy and particularly disorders of the heart system.

Imipramine is also not recommended if different types of drugs are being taken simultaneously, including barbiturates, monoamine oxidase inhibitors (MAOIs), SSRIs, lithium, methylphenidate, anticholinergics, or buspirone, the drug of choice for generalized anxiety disorder.

The use of imipramine is currently discouraged to some extent because of its pharmacological profile , which is difficult to tolerate for many people and very unspecific in terms of its effects on relevant neurotransmitters. However, it should also be noted that SSRIs and other modern antidepressants also cause significant adverse reactions.